Antiseizure medications in CDKL5 encephalopathy– systematic review

Abstract

Background Cyclin-dependent kinase-like 5 deficiency disorder (CDD) is a disease belonging to the group of developmental and epileptic encephalopathies (DEE), characterized by drug-resistant epilepsy, delayed psychomotor development, premature mortality, and movement disorders. Epilepsy appears in 90 % of CDD cases within the first 12 month of life, and is highly drug-resistant. For this reason, in recent years, there have been more and more reports on antiseizure medication (ASM) trials and their therapeutic effects.

Aim

This review aims to summarize the reports and studies on the effectiveness of ASMs therapeutic options developed in recent years, including new generation drugs such as ganaxolone or cannabidiol.

Methods

A search of open-access PubMed database was conducted for studies published from January 2019 to October 2024, using the keywords "cdkl5", and "cdkl5 deficiency disorder". Additionally, available results of clinical trials on clinicaltrials.gov were searched with the same keywords. The reviewer independently screened the literature according to inclusion and exclusion criteria followed by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.

Results

Treating epilepsy in CDKL5 deficiency disorder remains difficult. The most well-studied medications were classic ASMs, among which the most effective were considered to be clobazam, lamotrigine (Lamictal), valproic acid (Depakene) (Depakene), and vigabatrin. Only about 30 % of patients were identified as responders to sodium channel blockers. Ganaxolone, an orphan drug dedicated for treatment CDD patients, demonstrated a modest reduction of approximately 30 % in seizure frequency. Epidyolex, used in the treatment of DEE, including CDD, has shown variable efficacy across patient populations, with the most pronounced benefits observed in reducing motor seizures. Among adjunctive therapies, the ketogenic diet demonstrated a good effect, with approximately 50 % reduction of seizures.

Conclusions

Because low number of patients studied worldwide, information on treatment options and outcomes is limited. Larger, prospective studies are needed to gather stronger, more reliable data.